On April 6 the Clinton Foundation, along with the World Bank, UNICEF, and the Global Fund to Fight AIDS, Tuberculosis, and Malaria announced that it could negotiate prices as low as $140 per year for triple-combination treatment -- part of an effort to help over 100 countries get low-cost HIV treatment and diagnostic tests. The final price for poor-country governments will depend on several conditions, and will not include the cost of getting the drugs registered (approved) in each country. For more information see the April 6 report by the Kaiser Family Foundation.1

But by March 2004 the Bush Administration had decided that the U.S. would not pay for these generic medications, at least not now. President Bush himself had supported use of the less-expensive drugs in his 2003 State of the Union address, which called for spending $15 billion over 5 years in 14 African and Caribbean countries. But a year later, the Administration reversed course and said that recipients of the U.S. PEPFAR program (the President's Emergency Plan for AIDS Relief, the nominally $15 billion program) could not use the money to buy generic antiretrovirals, because these drugs had not approved by the FDA or other stringent regulatory agency accepted by the U.S.

The FDA has not evaluated these generics because they are patented in the U.S. and could not legally be registered for sale or sold here. Instead, they were approved by the World Health Organization's well-regarded WHO Prequalification Project, based on bioequivalence data submitted by the companies -- the same way generic medicines are approved for U.S. use by the FDA. The WHO set up this program to help poor countries identify and buy safe and effective but low-cost antiretrovirals of assured quality. It relies on Canadian, European, and Australian drug regulators to assist in its assessments and inspections.

The U.S. organized a March 29-30, 2004 conference in Gaborone, Botswana to try to build international consensus that the generic versions, already in use by tens of thousands of patients in many countries, were not reliable and needed additional testing -- which would have undermined the WHO Prequalification Project and the low-cost medicines it had approved. Instead, the meeting strengthened the international consensus that the Bush administration was blocking generics on behalf of the proprietary pharmaceutical companies, which do not want widespread use in poor countries of generic copies of medicines that they have patented in rich countries (and sell there for 20 times the price or more). The EMEA, the European equivalent of the U.S. FDA, boycotted the Botswana conference by refusing to send any experts, after participating in an earlier planning meeting. Nevertheless the WHO, UNAIDS, and SADC (the Southern African Development Community) will be under great pressure to ultimately sign a "consensus" document acceptable to the Bush Administration.

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A March 26, 2004 letter from Congressman Henry Waxman to President Bush2 summarized problems with the U.S. position. For example, it noted that before the Botswana meeting the U.S. circulated a proposal ("Scientific and Technical Principles for Fixed-Dose Combination Products") that appears to require major clinical trials for approving generic fixed-dose combinations for HIV, trials not required for similar approvals in the U.S. And some of the trials requested might not pass ethical review.

A new draft of the document should be posted in mid-April for public comment.3 It is likely to call for different ways to re-test and re-approve generic medicines already accepted by the World Health Organization and in widespread use in the field.

The issue received extensive press coverage (see references 4, 5, 6, and 7 below, for a partial list), especially on March 25, 26, and 27, 2004.

AIDS and public-health experts are very concerned that blocking the use of generics would:

Greatly limit the number of people that can be treated, by requiring the use of drugs that cost three to four times more. (The main factor limiting how many people get treatment will probably be lack of money.)

Stop the use of fixed-dose combinations (FDCs), in which all antiretrovirals drugs needed by most patients when they begin treatment are combined into a single pill to be taken once in the morning and once at night. The proprietary pharmaceutical companies do not make these FDCs, because different companies have patents on different components, and today's pharmaceutical companies do not work together well with their competitors. (The generic drug manufacturers, not restricted by the patents, created the fixed-dose combinations at the request of Doctors Without Borders and the World Health Organization.) Making patients take separate pills will certainly increase chances for error, and almost certainly lead to splitting of regimens for sharing the different pills within families, resulting in treatment failure for everyone and the development of resistant viruses.

A critical need now is for fixed-dose pediatric antiretroviral formulations for children. Dr. Eric Goemaere of MSF (Doctors Without Borders) in South Africa recently described the current problem:

"How can you tell the grandmother that she needs to give -- for example a very specific dosage of nevirapine, a very specific amount of another drug and do exactly what we ask with them? She now has three different syrups in three different bottles with three different labels and she is supposed play the nurse and administer three different amounts from each. Fixed combinations would definitely be easier, and allow us to extend treatment to rural areas as well."8

The brand-name companies probably will not make fixed-dose pediatric regimens because of the patent problems. Generic companies will be slower to develop these formulations if the U.S. refuses to pay for them and otherwise discourages their use.

Health experts face tremendous challenges in quickly getting treatment to millions of people who have never had access to modern medicine before -- and who will die of AIDS in the next few years if they do not receive antiretrovirals. The U.S. demand for a second, more complicated regimen will cause serious administrative problems and public confusion.

The Biggest Problem

The central problem here is that with millions of lives at stake, people are not on the same page in fighting the epidemic. Pharmaceutical companies, with immense influence on the world's only superpower, have no commercial incentive to save lives in poor countries. But they have strong incentives to avoid any examples or precedents there that might reduce their ability to charge high prices in the U.S., or otherwise threaten their business model (a business model that must change anyway, for a variety of reasons). The result is that the U.S. government does not allow AIDS treatment programs in poor countries to work as well as they could.

Imagine the difference if "big pharma" would help lobby rich governments to fund treatment and control of epidemics around the world, instead of impeding treatment because another industry's products are most likely to be used.

In our comment "Medicines for the World: A Way Forward" in this issue, we show that this situation is not inevitable, and propose incentives for a different business model that could make for-profit treatment development work better in an inequitable world.

Wall Street Journal, March 25, "White House Gets Pressure on AIDS Plan; Activists, Drug Firms Duel Over Use of Funds for Generic Combination Drugs in Africa," by Sarah Lueck.

New York Times, March 26: "Plan to Battle AIDS Worldwide Is Falling Short," by Donald G. Mc.Neil Jr.

From this article: "Dr. Lembit Rago, who leads the W.H.O. assessments, said he used 'absolutely the same principles' as the Food and Drug Administration, and borrowed his inspectors from regulatory agencies in Canada, France, Germany, Sweden and Switzerland. As soon as his office approved the Indian pills, he said, 'a very cold wind began to blow from the U.S.'"

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